The present invention relates to treatment of cardiovascular disease generally, and more particularly to treatment of atherosclerosis through adjunctive photodynamic therapy.
Atherosclerosis is a cardiovascular disease in which deposits of plaques (atheromas) containing cholesterol, lipid material, foam cells, lipophages, and proliferating smooth muscle cells are within the intima and media of large to small diameter arteries such as the aorta and the iliac, femoral, coronary, and cerebral arteries. The resultant stenosis causes reduction in blood flow.
Attempts to treat atherosclerosis have included bypass surgery wherein the diseased vascular segments are augmented by prosthetic or natural grafts. This procedure requires general anesthesia and a substantial healing period after surgery and, thus, is generally limited to cases of severe coronary artery disease.
Other approaches for primary treatment of stenotic vessels include percutaneous transluminal coronary angioplasty (PTCA), atherectomy, stenting and newer modalities of cardiovascular intervention including laser angioplasty. The primary drawbacks of these methods has been re-stenosis. Studies have shown that re-stenosis, or the re-narrowing of the internal lumen of an artery, subsequent to such primary treatment occurs in about 25-50% of cases where such primary treatment is performed. The result of re-stenosis is the requirement for an additional interventional or surgical procedure.
Various mechanisms can cause re-stenosis. One mechanism is rapid smooth muscle cell (SMC) proliferation at the lesion site. Smooth muscle cell proliferation is believed to occur immediately or at any time up to several hours after vessel wall injury that results from primary atherosclerotic treatment such as angioplasty. This proliferation continues for about 5-18 days depending on the individual. The cause of this rapid smooth muscle cell proliferation is believed to involve the release of various growth factors in response to the vessel wall injury. Specifically, after such vessel wall injury, some smooth muscle cells migrate to the intima where they are affected by the blood elements with which they come in contact, especially platelets and lipoproteins. Platelets contain a factor that stimulates smooth muscle cell proliferation and migration, which can result in re-stenosis.
Accordingly, there is a need to address the problem of smooth muscle cell proliferation in the treatment of atherosclerosis to minimize or eliminate the occurrence of re-stenosis.